Human T-cell lymphotropic virus types I and II (HTLV-I/-II) are genetically related oncornaviruses that share modes of transmission (breast feeding, sexual, and parenteral). HTLV-I is important in the etiology of cancer and other diseases, while HTLV-II's role in disease is uncertain. The Viral Epidemiology Branch (VEB) is studying HTLV-II in an endemic Native American population, the Guaymi Indians of Panama, among whom infection risk is strongly associated with older age and with indicators of sexual and mother-to-child transmission. HTLV-II has few clinical manifestations, but an increased risk of peripheral neuropathy has been noted in the Guaymi. Unlike HTLV-II, HTLV-I is strongly linked to adult T-cell leukemia/lymphoma (ATL), a highly fatal non-Hodgkin's lymphoma, and to a neurodegenerative disease termed HTLV-I-associated myelopathy (HAM). Because most infected people remain well, efforts are focused on identifying clinical and biologic markers of disease progression. Most ATL cases and nearly all pediatric HTLV-I infections result from prolonged breastfeeding, especially after age 6 months, and some children develop infective dermatitis, which may be a harbinger of ATL. Significant differences between subjects with ATL, those with HAM, and those with asymptomatic HTLV-I infection were found in serum markers of immune activation and in human leukocyte antigen types. VEB's large study of HTLV-I-infected families in Jamaica and Trinidad will use association and linkage analysis to clarify the relationships between host, environment, and disease manifestations of HTLV-I infection. To improve all HTLV-I/-II studies, a sensitive and specific assays has been developed to precisely quantify the number of blood cells infected with HTLV-I/-II ("proviral load").